Study of Pembrolizumab Following TACE in Primary Liver Carcinoma

NCT03397654 | Completed Phase 1 Results DMC

• 1 other identifier: PETAL1
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Open label, single arm, multi-centre study of pembrolizumab following trans-arterial chemoembolization (TACE). Twenty-six to 32 evaluable participants with primary liver cancer (hepatocellular cancer; HCC) will be assessed. The primary objective is to determine the safety and tolerability of pembrolizumab following TACE. The secondary objective is to evaluate the efficacy of pembrolizumab following TACE by improving progression-free survival rates as measured by modified response evaluation criteria in solid tumours (mRECIST) criteria.

Conditions

Primary Liver Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-emergent Adverse Events (Safety and Tolerability)

  The safety and tolerability of pembrolizumab will be assessed by recording the incidence of adverse events (AEs) using National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE v4).

  from the first pembrolizumab administration to up to 130 days after the last dose, 1.5 years

Secondary Outcomes (1)

• Progression-free Survival Rate (PFS; Efficacy) at 12 Weeks

  12 weeks

Study Arms (1)

TACE followed by pembrolizumab

EXPERIMENTAL

Trans-arterial chemoembolization (TACE) using doxorubicin solution (60 mg dose) and gelatin sponge particles; followed, at least 30 or 45 days later, by pembrolizumab solution (200 mg dose) every 3 weeks for a maximum of 1 year

Drug: Pembrolizumab; Combination Product: Trans-arterial chemoembolization

Interventions

Pembrolizumab DRUG

Pembrolizumab solution

Also known as: KEYTRUDA

TACE followed by pembrolizumab

Trans-arterial chemoembolization COMBINATION_PRODUCT

Doxorubicin injected through the hepatic blood supply directly to the cancer-affected part of the liver, then gelatin sponge particles injected to block the blood vessels supplying the tumour

Also known as: TACE

TACE followed by pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Be willing to provide tissue from an excisional biopsy of a tumour lesion.
• Have at least one uni-dimensional lesion measurable by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI) based on mRECIST criteria.
• Be ineligible for surgical resection or liver transplantation.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Demonstrate adequate organ function
• Have an overall Child-Pugh score \<7
• Female subject of childbearing potential should have a negative urine or serum pregnancy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Women of childbearing potential must be willing to use a highly effective method of contraception as outlined in Section 6.9.2 for the course of the study through 120 days after the last dose of Investigational Medicinal Product (IMP). Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Sexually active males must agree to use an adequate method of contraception as outlined in Section 6.9.2 starting with the first dose of IMP through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Has extrahepatic metastasis.
• Prior TACE or systemic anticancer treatment for HCC.
• Has any contraindication for TACE including portosystemic shunt, hepatofugal blood flow, known severe atheromatosis.
• Has history of bleeding within the 4 weeks preceding study enrolment.
• Has hepatic encephalopathy.
• Has ascites that is refractory to diuretic therapy.
• Is currently participating and receiving therapy or has participated or is participating in a study of an IMP or used an investigational device within 4 weeks of the first dose of IMP.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy.
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to Pembrolizumab or any of its excipients.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy. Exceptions relating to Hepatitis B and C virus infection are documented in Section 5.3.1, Table 5.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Principal Investigator (PI).

Sponsors & Collaborators

• Imperial College London: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Related Publications (1)

• Fessas P, Scheiner B, D'Alessio A, M Fulgenzi CA, Korolewicz J, Ward C, Tait P, Thomas R, Cortellini A, Sharma R, Pinato DJ. PETAL protocol: a phase Ib study of pembrolizumab after transarterial chemoembolization in hepatocellular carcinoma. Future Oncol. 2023 Mar;19(7):499-507. doi: 10.2217/fon-2022-0916. Epub 2023 Apr 25.

  PMID: 37097715 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

Limitations include, limited sample size, lack of control arm and the Impact of Coronavirus disease pandemic, which made recruitment and retention of participants to the investigator-led clinical trial difficult, leading to reduction in the number of sample available for translational analysis.

Results Point of Contact

• Title: Dr David Pinato
• Organization: Imperial College London

david.pinato@imperial.ac.uk

+44 20 7594 2799

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: January 12, 2018
• Study Start: January 28, 2018
• Primary Completion: February 1, 2023
• Study Completion: March 23, 2023
• Last Updated: March 6, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)